Dr Sakr and colleagues [1] report a single centre cohort study evaluating the relationship between anaemia, blood transfusions and mortality in patients admitted to a surgical ICU.. Howe
Trang 1Dr Sakr and colleagues [1] report a single centre cohort
study evaluating the relationship between anaemia, blood
transfusions and mortality in patients admitted to a
surgical ICU Th e authors report some fi ndings that are
not new or surprising, namely that anaemia is associated
with adverse patient outcomes However, when they
performed multivariate analyses with adjustment for
potential confounders to the blood transfusion/patient
outcomes relationship they found that transfusions were
associated with lower patient mortality, especially among
older sicker patients At face value this contradicts the
majority of previous cohort studies [2] and the only large
randomised trial of diff erent transfusion triggers in
critically ill patients (the Canadian Critical Care Trials
Group’s ‘Transfusion requirements in critical care’
(TRICC) trial) [3] Th e authors’ fi ndings raise a number
of questions, including: does this association indicate
cause and eff ect’? Are the fi ndings of the TRICC trial
generalisable to intensive care patients today? And,
perhaps most importantly, should we use blood more
liberally in critically ill patients than the TRICC trial and
our current guidelines suggest?
Does this association indicate ‘cause and eff ect’?
Although it is possible to perform complex statistical adjustments for potential confounders in cohort studies
to try to clarify the true relationship between a variable
or intervention of interest and an outcome, this is notoriously problematic, especially in relation to blood transfusions [4] Adjustments can be made for measured factors, but there is always the possibility of residual confounding from ‘unknowns’, which is more likely in complex heterogeneous populations ICU populations are highly heterogeneous at multiple levels, including pre-illness co-morbidity, diagnosis requiring admission, early illness severity, and subsequent complications, to name a few Dr Sakr and colleagues included adjustment for some factors but, as they acknowledge, it is very likely there were many ‘unknowns’ that were potentially rele-vant Bias by indication is very likely in this sort of analysis whereby factors aff ecting a clinical decision (blood transfusion in this case) cannot be adequately captured
or adjusted for, thereby introducing an imbalance Dr Sakr and colleagues used propensity analysis in an attempt to overcome this problem, which attempts to produce matched pairs from observational data to simulate a ‘virtual’ randomised trial Th e limitations of this approach have been previously discussed in detail in relation to another cohort study involving some of these authors [5,6] Although the chance of erroneous asso-ciations is probably reduced, the problem remains that the patients being matched may diff er in unmeasured ways Th is might be more likely in a single centre study, such as the one performed by Dr Sakr and colleagues, where transfusion decision-making was presumably more consistent Th e mean hemoglobin transfusion trigger was 8.2 g/dL and in 30% of cases it was >9 g/dL, so this ICU was signifi cantly more liberal than the restrictive arm of the TRICC trial [3] Another issue is that there was no information about the indications for transfusion, especially bleeding, which could have created imbalance between the matched pairs In short, we cannot be sure
of causality between blood transfusions and better outcomes, but the study does stimulate us to look again
at the TRICC trial and its relevance today
Abstract
Current evidence suggests that critically ill patients
tolerate anaemia well and that blood transfusions
may increase the risk of adverse outcomes Dr Sakr
and colleagues present a contradictory analysis of a
surgical ICU cohort, fi nding an association between
blood transfusions and lower hospital mortality after
adjustment for a range of potential confounders
Analyses of this kind are interesting and provocative,
but are limited by residual confounding and bias by
indication The data emphasise the need for additional
high quality trials of transfusion practice in critical care
© 2010 BioMed Central Ltd
Red cell transfusion triggers in critically ill patients: time for some new TRICCs?
Timothy S Walsh*
See related research by Sakr et al., http://ccforum.com/content/14/3/R92
C O M M E N TA R Y
*Correspondence: twalsh@staff mail.ed.ac.uk
Anaesthetics, Critical Care and Pain Medicine, Royal Infi rmary of Edinburgh, Little
France Crescent, Edinburgh EH16 2SA, UK
Walsh Critical Care 2010, 14:170
http://ccforum.com/content/14/3/170
© 2010 BioMed Central Ltd
Trang 2Are the fi ndings of the TRICC trial generalisable to
intensive care patients today?
Th e TRICC trial found that mortality was higher in
younger patients (aged <55 years) and those with
APACHE II scores <20 when blood was used liberally [3]
Treatment eff ects were similar for older patients and
those with APACHE II scores ≥20, and in subgroup
analyses no strong signals favouring either group were
found in relation to duration of mechanical ventilation
[7], or trauma diagnosis [8] Patients with ischemic heart
disease as a baseline comorbidity had a trend towards
better outcome with more liberal blood use [9] and a
later analysis highlighted the potential interaction
between ischemic heart disease and the hemoglobin level
maintained in intensive care, which could have been
underestimated in the original trial report [10] All of
these subgroup analyses were underpowered, and even
the full trial was much smaller than intended (the
intended sample size was 1,620; achieved was 838)
Another relevant factor was that clinicians declined to
enrol 29% of eligible patients Th ese issues raise the
possibility that diff erent treatment eff ects might exist for
patients with ischemic heart disease, and among older
and/or sicker patients, especially those with evidence of
inadequate oxygen delivery or delayed weaning from
mechanical ventilation Th ese uncertainties are
acknow-ledged in recent guidelines and systematic reviews
[11,12], and it is perhaps not surprising that surveys
indicate continued variation in clinical practice [11,13]
Th e other key uncertainty relates to the impact of
pre-storage leucodepletion, which was not used during the
TRICC trial, but is now undertaken routinely in most
developed countries Th is additional processing step was
associated with small (1% absolute risk reduction) but
signifi cant ICU mortality reduction in Canada, and may
be particularly important with prolonged red cell storage
[14,15]
Should we use blood more liberally in critically
ill patients than the TRICC trial and our current
guidelines suggest?
Th e answer to this question for younger, less severely
unwell patients is surely NO For other patients we need
to continue to use clinical judgement, but the evidence is
still most consistent with a target haemoglobin
concen-tration of <9 g/dL, especially given the potential risks of
blood transfusions and uncertain eff ectiveness of stored
red cells [11,15] Given our recent experiences of
thera-peutic strategies with early promise, but for which later
trials showed confl icting safety data either overall (for
example, tight glycaemic control) or in patient subgroups
(for example, activated protein C), it is surely time for a
‘new TRICC’ Only well designed randomised trials will
improve our confi dence in making transfusion decisions
Unfortunately, studies such as the one performed by Dr Sakr and colleagues simply add to our uncertainty
Abbreviations
TRICC = Transfusion requirements in critical care.
Competing interests
The author declares that he has no competing interests.
Published: 23 June 2010
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doi:10.1186/cc9043
Cite this article as: Walsh TS: Red cell transfusion triggers in critically ill
patients: time for some new TRICCs? Critical Care 2010, 14:170.
Walsh Critical Care 2010, 14:170
http://ccforum.com/content/14/3/170
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